The regulation of the pineal gland by environmental and physiological factors is analyzed, exclusive of transmembrane and intracellular regulatory mechanisms (see Z01 HD 00095-22 LDN). The pineal gland is part of the melatonin rhythm generating system, a neural circuit which includes a circadian clock in the suprachiasmatic nucleus (SCN); the SCN is reset and entrained by light acting through the eye. An area of special current interest is proteins involved in transmembrane signal processing. These include G-proteins, MEKA and the S-antigen. These studies indicate that MEKA and the S-antigen are absent before birth and appear rapidly during the first postnatal week in the rat. In contrast, Gbeta is present at adult levels prior to birth. In the adult, it has been found that the amount of MEKA and the Phosphorylation state of this enzyme are regulated by environmental lighting. Total MEKA increases at night; phosphorylation also increases at night in the dark and the protein is rapidly dephosphorylated by exposure to light. An interesting new finding is that the amount of pineal Gsalpha is under impressive regulation, increasing following procedures which block neural stimulation. In addition, the large and small splice variants of Gsalpha exhibit different developmental patterns. It has also been discovered that the developmental appearance of the adrenergic stimulation of pineal cyclic GMP occurs several weeks after that of the adrenergic stimulation of cyclic GMP.